tbuckley/cabot-search huggingface dataset:
Evaluating the Evidence for Brain-Based Biotypes of Psychiatric Vulnerability in the Acute Aftermath of Trauma
Authors: Ziv Ben-Zion, Tobias R. Spiller, Jackob N. Keynan, Roee Admon, Ifat Levy, Israel Liberzon, Arieh Y. Shalev, Talma Hendler, Ilan Harpaz-Rotem
Journal: American Journal of Psychiatry (2023)

Objective: The weak link between subjective symptom-based diagnostic methods for posttraumatic psychopathology and objectively measured neurobiological indices forms a barrier to the development of effective personalized treatments. To overcome this problem, recent studies have aimed to stratify psychiatric disorders by identifying consistent subgroups based on objective neural markers. Along these lines, a promising 2021 study by Stevens et al. identified distinct brain-based biotypes associated with different longitudinal patterns of posttraumatic symptoms. Here, the authors conducted a conceptual nonexact replication of that study using a comparable data set from a multimodal longitudinal study of recent trauma survivors. Methods: A total of 130 participants (mean age, 33.61 years, SD=11.21; 48% women) admitted to a general hospital emergency department following trauma exposure underwent demographic, clinical, and neuroimaging assessments 1, 6, and 14 months after trauma. All analyses followed the pipeline outlined in the original study and were conducted in collaboration with its authors. Results: Task-based functional MRI conducted 1 month posttrauma was used to identify four clusters of individuals based on profiles of neural activity reflecting threat and reward reactivity. These clusters were not identical to the previously identified brain-based biotypes and were not associated with prospective symptoms of posttraumatic psychopathology. Conclusions: Overall, these findings suggest that the original brain-based biotypes of trauma resilience and psychopathology may not generalize to other populations. Thus, caution is warranted when attempting to define subtypes of psychiatric vulnerability using neural indices before treatment implications can be fully realized. Additional replication studies are needed to identify more stable and generalizable neuroimaging-based biotypes of posttraumatic psychopathology.
Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case–control study
Authors: Thiago Cerqueira-Silva, Syed Ahmar Shah, Chris Robertson, Mauro Sanchez, Srinivasa Vittal Katikireddi, Vinicius de Araujo Oliveira, Enny S. Paixão, Igor Rudan, Juracy Bertoldo Junior, Gerson O. Penna, Neil Pearce, Guilherme Loureiro Werneck, Mauricio L. Barreto, Viviane S. Boaventura, Aziz Sheikh, Manoel Barral-Netto
Journal: PLoS Medicine (2023)

Background Brazil and Scotland have used mRNA boosters in their respective populations since September 2021, with Omicron’s emergence accelerating their booster program. Despite this, both countries have reported substantial recent increases in Coronavirus Disease 2019 (COVID-19) cases. The duration of the protection conferred by the booster dose against symptomatic Omicron cases and severe outcomes is unclear. Methods and findings Using a test-negative design, we analyzed national databases to estimate the vaccine effectiveness (VE) of a primary series (with ChAdOx1 or BNT162b2) plus an mRNA vaccine booster (with BNT162b2 or mRNA-1273) against symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death) during the period of Omicron dominance in Brazil and Scotland compared to unvaccinated individuals. Additional analyses included stratification by age group (18 to 49, 50 to 64, ≥65). All individuals aged 18 years or older who reported acute respiratory illness symptoms and tested for SARS-CoV-2 infection between January 1, 2022, and April 23, 2022, in Brazil and Scotland were eligible for the study. At 14 to 29 days after the mRNA booster, the VE against symptomatic SARS-CoV-2 infection of ChAdOx1 plus BNT162b2 booster was 51.6%, (95% confidence interval (CI): [51.0, 52.2], p &lt; 0.001) in Brazil and 67.1% (95% CI [65.5, 68.5], p &lt; 0.001) in Scotland. At ≥4 months, protection against symptomatic infection waned to 4.2% (95% CI [0.7, 7.6], p = 0.02) in Brazil and 37.4% (95% CI [33.8, 40.9], p &lt; 0.001) in Scotland. VE against severe outcomes in Brazil was 93.5% (95% CI [93.0, 94.0], p &lt; 0.001) at 14 to 29 days post-booster, decreasing to 82.3% (95% CI [79.7, 84.7], p &lt; 0.001) and 98.3% (95% CI [87.3, 99.8], p &lt; 0.001) to 77.8% (95% CI [51.4, 89.9], p &lt; 0.001) in Scotland for the same periods. Similar results were obtained with the primary series of BNT162b2 plus homologous booster. Potential limitations of this study were that we assumed that all cases included in the analysis were due to the Omicron variant based on the period of dominance and the limited follow-up time since the booster dose. Conclusions We observed that mRNA boosters after a primary vaccination course with either mRNA or viral-vector vaccines provided modest, short-lived protection against symptomatic infection with Omicron but substantial and more sustained protection against severe COVID-19 outcomes for at least 3 months.
Nonhealing Genital Ulcers as Clue to a Multisystem Disease
Authors: Anubha Dev, Debajyoti Chatterjee, Keshavamurthy Vinay
Journal: JAMA Dermatology (2023)

A female patient in her late 40s presented with a 3-year history of nonhealing ulcers in her groin and axillae. What is your diagnosis?
Conventional type 1 dendritic cells protect against gut barrier disruption via maintaining Akkermansia muciniphila in alcoholic steatohepatitis
Authors: Liuyi Hao, Wei Zhong, Jongmin Woo, Xiaoyuan Wei, Hao Ma, Haibo Dong, Wei Guo, Xinguo Sun, Ruichao Yue, Jiangchao Zhao, Qibin Zhang, Zhanxiang Zhou
Journal: Hepatology (2023)

Background and Aims: Alcohol-perturbed gut immune homeostasis is associated with the development of alcoholic liver disease (ALD). However, the role of intestinal dendritic cells (DCs) in ALD progression is still unknown. This study aimed to investigate the cellular and molecular mechanisms through which intestinal DCs respond to alcohol exposure and contribute to the pathogenesis of ALD. Approach and Results: After 8 weeks of alcohol consumption, the number of basic leucine zipper transcription factor ATF-like 3 ( Batf3 )-dependent conventional type 1 DCs (cDC1s) was dramatically decreased in the intestine but not the liver. cDC1 deficient Batf3 knockout mice along with wild-type mice were subjected to chronic-binge ethanol feeding to determine the role of intestinal cDC1s reduction in ALD. cDC1s deficiency exacerbated alcohol-induced gut barrier disruption, bacterial endotoxin translocation into the circulation, and liver injury. Adoptive transfer of cDC1s to alcohol-fed mice ameliorated alcohol-mediated gut barrier dysfunction and liver injury. Further studies revealed that intestinal cDC1s serve as a positive regulator of Akkermansia muciniphila ( A. muciniphila ). Oral administration of A. muciniphila markedly reversed alcoholic steatohepatitis in mice. Mechanistic studies revealed that cDC1s depletion exacerbated alcohol-downregulated intestinal antimicrobial peptides which play a crucial role in maintaining A. muciniphila abundance, by disrupting the IL-12-interferon gamma signaling pathway. Lastly, we identified that intestinal cDC1s were required for the protective role of Lactobacillus reuteri in alcoholic steatohepatitis. Conclusions: This study demonstrated that cDC1s protect alcohol-induced liver injury by maintaining A. muciniphila abundance in mice. Targeting cDC1s may serve as a promising therapeutic approach for treating ALD.
Letter to the Editor: Is embolization of large spontaneous shunt effective in the prevention of HE after TIPS?
Authors: Gin-Ho Lo
Journal: Hepatology (2023)

To the editor, I read with interest regarding concurrent large spontaneous portosystemic shunt embolization for the prevention of HE after TIPS.1 Though inspiring, some points need further clarification. TIPS is well documented to be effective in the prevention of variceal rebleeding.2 However, owing to associated with complications such as HE, TIPS is only recommended in patients that failed first-line therapy with combination of nonselective beta blockers and banding ligation.3,4 In the trial by Lv and colleagues, it appeared that TIPS was the first-line therapy to prevent variceal rebleeding or even primary prophylaxis. This was not in accordance with current practice guidelines.4 Three patients with prior history of HE were enrolled in the group of TIPS alone; this surely could increase its incidence of HE. Moreover, 2 patients in the group of TIPS alone versus 4 patients in the group of TIPS plus embolization died. Though statistically insignificant, this implied that TIPS could not improve the survival in these patients by additional embolization of concurrent large spontaneous portosystemic shunt. Since TIPS plus embolization of concurrent large spontaneous shunt could not completely eliminate the risk of HE in these patients, it is interesting that the authors suggested rifaximin administration after the procedure. In our own experience, the use of lactulose could also be effective in the prevention of HE after TIPS.5 CONFLICT OF INTEREST The author has no conflicts to report.
Jump-starting the Journey to Transesophageal Echocardiogram Mastery
Authors: Michael Spooner, Kathryn Berlacher
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Adult Low-Hypodiploid Acute Lymphoblastic Leukemia Emerges from Preleukemic<i>TP53</i>-Mutant Clonal Hematopoiesis
Authors: Rathana Kim, Hugo Bergugnat, Lise Larcher, Matthieu Duchmann, Marie Passet, Stéphanie Gachet, Wendy Cuccuini, Marina Lafage-Pochitaloff, Cédric Pastoret, Nathalie Grardel, Vahid Asnafi, Beat W. Schäfer, Eric Delabesse, Raphaël Itzykson, Lionel Adès, Yosr Hicheri, Yves Chalandon, Carlos Graux, Patrice Chevallier, Mathilde Hunault, Thibaut Leguay, Françoise Huguet, Véronique Lhéritier, Hervé Dombret, Jean Soulier, Philippe Rousselot, Nicolas Boissel, Emmanuelle Clappier
Journal: Blood Cancer Discovery (2023)

Abstract Low hypodiploidy defines a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL) with a dismal outcome. To investigate the genomic basis of low-hypodiploid ALL (LH-ALL) in adults, we analyzed copy-number aberrations, loss of heterozygosity, mutations, and cytogenetics data in a prospective cohort of Philadelphia (Ph)-negative B-ALL patients (n = 591, ages 18–84 years), allowing us to identify 80 LH-ALL cases (14%). Genomic analysis was critical for evidencing low hypodiploidy in many cases missed by cytogenetics. The proportion of LH-ALL within Ph-negative B-ALL dramatically increased with age, from 3% in the youngest patients (under 40 years old) to 32% in the oldest (over 55 years old). Somatic TP53 biallelic inactivation was the hallmark of adult LH-ALL, present in virtually all cases (98%). Strikingly, we detected TP53 mutations in posttreatment remission samples in 34% of patients. Single-cell proteogenomics of diagnosis and remission bone marrow samples evidenced a preleukemic, multilineage, TP53-mutant clone, reminiscent of age-related clonal hematopoiesis. Significance: We show that low-hypodiploid ALL is a frequent entity within B-ALL in older adults, relying on somatic TP53 biallelic alteration. Our study unveils a link between aging and low-hypodiploid ALL, with TP53-mutant clonal hematopoiesis representing a preleukemic reservoir that can give rise to aneuploidy and B-ALL. See related commentary by Saiki and Ogawa, p. 102. This article is highlighted in the In This Issue feature, p. 101
Prostate cancer disparities among American Indians and Alaskan Natives in the United States
Authors: Carissa E Chu, Michael S Leapman, Shoujun Zhao, Janet E Cowan, Samuel L Washington, Matthew R Cooperberg
Journal: JNCI Journal of the National Cancer Institute (2023)

Americans Indians and Alaska Natives face disparities in cancer care with lower rates of screening, limited treatment access, and worse survival. Prostate cancer treatment access and patterns of care remain unknown.
Spotlighting cellular therapies to advance the treatment of medulloblastoma
Authors: John A Ligon, Elias J Sayour
Journal: Neuro-Oncology (2023)

Journal Article Spotlighting cellular therapies to advance the treatment of medulloblastoma Get access John A Ligon, John A Ligon Department of Pediatrics, Division of Hematology/Oncology, University of Florida, Gainesville, FL, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Elias J Sayour Elias J Sayour Department of Neurosurgery, University of Florida, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Gainesville, FL, USA Corresponding Author: Elias Sayour, MD, PhD, Department of Neurosurgery, University of Florida, PO Box 100265, Gainesville, FL 32610-0265, USA (elias.sayour@neurosurgery.ufl.edu). Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 4, April 2023, Pages 628–630, https://doi.org/10.1093/neuonc/noad005 Published: 11 January 2023 Article history Published: 11 January 2023 Corrected and typeset: 03 February 2023
Adding device identifiers to claims forms—a key step to advance medical device safety
Authors: Kushal T. Kadakia, Sanket S. Dhruva, Joseph S. Ross, Harlan M. Krumholz
Journal: BMJ (2023)

A key US government advisory group should endorse a proposal to allow medical devices to be tracked on claims forms, argue <b>Kushal T. Kadakia</b>, <b>Sanket S. Dhruva</b>, <b>Joseph S. Ross</b>, and <b>Harlan Krumholz</b>.
Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma
Authors: Keiji Kurata, Anna James-Bott, Mark A. Tye, Leona Yamamoto, Mehmet K. Samur, Yu-Tzu Tai, James Dunford, Catrine Johansson, Filiz Senbabaoglu, Martin Philpott, Charlotte Palmer, Karthik Ramasamy, Sarah Gooding, Mihaela Smilova, Giorgia Gaeta, Manman Guo, John C. Christianson, N. Connor Payne, Kritika Singh, Kubra Karagoz, Matthew E. Stokes, Maria Ortiz, Patrick Hagner, Anjan Thakurta, Adam Cribbs, Ralph Mazitschek, Teru Hideshima, Kenneth C. Anderson, Udo Oppermann
Journal: Blood Cancer Journal (2023)

Abstract Multiple myeloma (MM) is a plasma cell malignancy characterised by aberrant production of immunoglobulins requiring survival mechanisms to adapt to proteotoxic stress. We here show that glutamyl-prolyl-tRNA synthetase (GluProRS) inhibition constitutes a novel therapeutic target. Genomic data suggest that GluProRS promotes disease progression and is associated with poor prognosis, while downregulation in MM cells triggers apoptosis. We developed NCP26, a novel ATP-competitive ProRS inhibitor that demonstrates significant anti-tumour activity in multiple in vitro and in vivo systems and overcomes metabolic adaptation observed with other inhibitor chemotypes. We demonstrate a complex phenotypic response involving protein quality control mechanisms that centers around the ribosome as an integrating hub. Using systems approaches, we identified multiple downregulated proline-rich motif-containing proteins as downstream effectors. These include CD138, transcription factors such as MYC, and transcription factor 3 (TCF3), which we establish as a novel determinant in MM pathobiology through functional and genomic validation. Our preclinical data therefore provide evidence that blockade of prolyl-aminoacylation evokes a complex pro-apoptotic response beyond the canonical integrated stress response and establish a framework for its evaluation in a clinical setting.
Extreme body mass index and survival in newly diagnosed multiple myeloma patients
Authors: Urvi A. Shah, Karissa Whiting, Sean Devlin, Rachel Ershler, Bindu Kanapuru, David J. Lee, Sabrin Tahri, Thomas Gwise, Even H. Rustad, Sham Mailankody, Alexander M. Lesokhin, Dickran Kazandjian, Francesco Maura, Daniel Auclair, Brenda M. Birmann, Saad Z. Usmani, Nicole Gormley, Catherine R. Marinac, Ola Landgren
Journal: Blood Cancer Journal (2023)
A pooled analysis of outcomes according to cytogenetic abnormalities in patients receiving ixazomib- vs placebo-based therapy for multiple myeloma
Authors: Wee-Joo Chng, Sagar Lonial, Gareth J. Morgan, Shinsuke Iida, Philippe Moreau, Shaji K. Kumar, Philip Twumasi-Ankrah, Miguel Villarreal, Ajeeta B. Dash, Alexander Vorog, Xiaoquan Zhang, Kaveri Suryanarayan, Richard Labotka, Meletios A. Dimopoulos, S. Vincent Rajkumar
Journal: Blood Cancer Journal (2023)

Abstract Some cytogenetic abnormalities (CAs) are associated with poorer prognosis in multiple myeloma (MM); proteasome inhibitors appear to benefit patients with high-risk CAs. We evaluated 2247 MM patients from the TOURMALINE-MM1/-MM2/-MM3/-MM4 trials to assess the PFS benefit of ixazomib plus lenalidomide-dexamethasone (Rd) vs placebo-Rd (TOURMALINE-MM1/-MM2) or ixazomib vs placebo (TOURMALINE-MM3/-MM4) in specific high-risk CAs. After a pooled median follow-up of 25.6 months, the hazard ratio (HR) for PFS with ixazomib- vs placebo-based therapy for high-risk patients was 0.74 (95% confidence interval [CI]: 0.59–0.93; median PFS [mPFS] 17.8 vs 13.2 months), and 0.70 (95% CI: 0.62–0.80; mPFS 26.3 vs 17.6 months) for complementary standard-risk patients. The HR for expanded high-risk patients was 0.75 (95% CI: 0.64–0.87; mPFS 18.1 vs 14.1 months), and 0.71 (95% CI: 0.59–0.85; mPFS 36.1 vs 21.4 months) for complementary standard-risk patients. The HR for PFS with ixazomib- vs placebo-based therapy was 0.68 in patients with t(4;14) (95% CI: 0.48–0.96; mPFS 22.4 vs 13.2 months), and 0.77 for patients with amp1q21 (95% CI: 0.63–0.93; mPFS 18.8 vs 14.5 months). A PFS benefit was demonstrated with ixazomib- vs placebo-based therapy regardless of cytogenetic status, with greatest benefit observed in patients with t(4;14) and amp1q21.
OOCDB: A Comprehensive, Systematic, and Real-Time Organs-on-a-Chip Database
Authors: Jian Li, Weicheng Liang, Zaozao Chen, Xingyu Li, Pan Gu, Anna Liu, Pin Chen, Qiwei Li, Xueyin Mei, Jing Yang, Jun Liu, Lincao Jiang, Zhongze Gu
Journal: Genomics Proteomics & Bioinformatics (2023)

Organs-on-a-chip is a microfluidic microphysiological system that uses microfluidic technology to analyze the structure and function of living human cells at the tissue and organ levels in vitro. Organs-on-a-chip technology, as opposed to traditional two-dimensional cell culture and animal models, can more closely simulate pathologic and toxicologic interactions between different organs or tissues and reflect the collaborative response of multiple organs to drugs. Despite the fact that many organs-on-a-chip-related data have been published, none of the current databases have all of the following functions: searching, downloading, as well as analyzing data and results from the literature on organs-on-a-chip. Therefore, we created an organs-on-a-chip database (OOCDB) as a platform to integrate information about organs-on-a-chip from various sources, including literature, patents, raw data from microarray and transcriptome sequencing, several open-access datasets of organs-on-a-chip and organoids, and data generated in our laboratory. OOCDB contains dozens of sub-databases and analysis tools, and each sub-database contains various data associated with organs-on-a-chip, with the goal of providing researchers with a comprehensive, systematic, and convenient search engine. Furthermore, it offers a variety of other functions, such as mathematical modeling, three-dimensional modeling, and citation mapping, to meet the needs of researchers and promote the development of organs-on-a-chip. The OOCDB is available at http://www.organchip.cn.
Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure
Authors: Wanhao Yan, Xiao Lin, Yiqian Ying, Jun Li, Zhipeng Fan
Journal: International Journal of Oral Science (2023)

The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the "m6A site methylation stoichiometry" of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3'-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.
A novel heterologous receptor-binding domain dodecamer universal mRNA vaccine against SARS-CoV-2 variants
Authors: Shugang Qin, Hai Huang, Wen Xiao, Kepan Chen, Xi He, Xiaoshan Tang, Zhiying Huang, Yupei Zhang, Xing Duan, Na Fan, Qian Zheng, Min Wu, Guangwen Lu, Yuquan Wei, Xiawei Wei, Xiangrong Song
Journal: Acta Pharmaceutica Sinica B (2023)

There are currently approximately 4,000 mutations in the SARS-CoV-2 S protein gene and emerging SARS-CoV-2 variants continue to spread rapidly worldwide. Universal vaccines with high efficacy and safety urgently need to be developed to prevent SARS-CoV-2 variants pandemic. Here, we described a novel self-assembling universal mRNA vaccine containing a heterologous receptor-binding domain (HRBD)-based dodecamer (HRBD